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  2. Cell Cycle/DNA Damage Stem Cell/Wnt
  3. Casein Kinase
  4. SR-3029

SR-3029 是一種有效的，ATP 競(jìng)爭(zhēng)性的 CK1δ 和 CK1ε 的抑制劑，IC50 值分別為 44 nM 和 260 nM，Ki 均為 97 nM。

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SR-3029 Chemical Structure

SR-3029 Chemical Structure

CAS No. : 1454585-06-8

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規(guī)格 價(jià)格 是否有貨 數(shù)量
10 mM * 1 mL in DMSO ￥1268
In-stock
1 mg ￥480
In-stock
5 mg ￥1200
In-stock
10 mg ￥1900
In-stock
25 mg ￥3800
In-stock
50 mg ￥5447
In-stock
100 mg 現(xiàn)貨 詢價(jià)
200 mg   詢價(jià)  
500 mg   詢價(jià)  

* Please select Quantity before adding items.

Customer Review

WB
RT-PCR
IHC

    SR-3029 purchased from MCE. Usage Cited in: Proc Natl Acad Sci U S A. 2018 Aug 7;115(32):E7522-E7531.   [Abstract]

    TPA induces the phosphorylation of LRP6 and the formation of a CK1ε-LRP6-axin1 complex. (A) HEK293T and UACC903 cells cotransfected with CK1ε-GFP and LRP6 expression vectors are treated with 10 nM TPA for 6 h. Cell lysates are analyzed by immunoblotting. (B) HEK293T and UACC903 cells transfected with a CK1εexpression plasmid ae treated with or without 10 nM TPA for 6 h. (C) UACC903 cells are incubated with 10 nM TPA in the presence or absence of 60 nM SR3029 for 6 h.

    SR-3029 purchased from MCE. Usage Cited in: Proc Natl Acad Sci U S A. 2018 Aug 7;115(32):E7522-E7531.   [Abstract]

    SR3029 suppresses TPA-induced skin tumor formation in vivo via blockade of Wnt/β-catenin signaling in mouse skin two-stage chemical carcinogenesis. Fifteen mice per group are initiated with DMBA, followed by repetitive applications of TPA alone or together with SR3029 in acetone twice a week for 18 wk. Hematoxylin/eosin staining and immunohistochemistry staining using antibodies specific for Ki-67, β-catenin, active β-catenin, CK1ε, and CK1δ.

    SR-3029 purchased from MCE. Usage Cited in: Proc Natl Acad Sci U S A. 2018 Aug 7;115(32):E7522-E7531.   [Abstract]

    SR3029 suppresses TPA-induced skin tumor formation in vivo via blockade of Wnt/β-catenin signaling in mouse skin two-stage chemical carcinogenesis. Fifteen mice per group are initiated with DMBA, followed by repetitive applications of TPA alone or together with SR3029 in acetone twice a week for 18 wk. Expression levels of β-catenin, active β-catenin, CK1ε, CK1δ, and LRP6 in tumor samples are visualized after immunoblotting.

    SR-3029 purchased from MCE. Usage Cited in: Proc Natl Acad Sci U S A. 2018 Aug 7;115(32):E7522-E7531.   [Abstract]

    TPA increases the expression of Wnt target genes. HEK293T and UACC903 cells are treated for 24 h with or without 10 nM TPA in the presence or absence of increasing concentrations of SR3029 as indicated. Quantitative PCR analysis is conducted to detect the mRNA expression of CD44, cyclin D1, and DKK1.

    SR-3029 purchased from MCE. Usage Cited in: Proc Natl Acad Sci U S A. 2018 Aug 7;115(32):E7522-E7531.   [Abstract]

    SR3029 suppresses TPA-induced skin tumor formation in vivo via blockade of Wnt/β-catenin signaling in mouse skin two-stage chemical carcinogenesis. Fifteen mice per group are initiated with DMBA, followed by repetitive applications of TPA alone or together with SR3029 in acetone twice a week for 18 wk. The mRNA expression levels of CD44, cyclin D1, and Fosb in tumor tissuesare quantitated by real-time PCR.

    查看 Casein Kinase 亞型特異性產(chǎn)品:

    • 生物活性

    • 實(shí)驗(yàn)參考方法

    • 純度 & 產(chǎn)品資料

    • 參考文獻(xiàn)

    生物活性

    SR-3029 is a potent and ATP competitive CK1δ and CK1ε inhibitor, with IC50s of 44 nM and 260 nM, respectively, and Kis of 97 nM for both kinases.

    IC50 & Target[1]

    CKIδ

    44 nM (IC50)

    CDK6/cyclin D3

    427 nM (IC50)

    CDK6/cyclin D1

    428 nM (IC50)

    CDK4/cyclin D3

    368 nM (IC50)

    CDK4/cyclin D1

    576 nM (IC50)

    FLT3

    3000 nM (IC50)

    細(xì)胞效力
    (Cellular Effect)
    Cell Line Type Value Description References
    MDA-MB-231 EC50
    26 nM
    Compound: 13; SR-3029
    Antiproliferative activity against human MDA-MB-231 cells after 72 hrs by CellTiter-Glo assay
    Antiproliferative activity against human MDA-MB-231 cells after 72 hrs by CellTiter-Glo assay
    		[PMID: 29289448]
    體外研究
    (In Vitro)

    SR-3029 is a potent CK1δ/CK1ε inhibitor, with IC50s of 44 nM and 260 nM, respectively. SR-3029 is ATP competitive, with Kis of 97 nM for CK1δ/CK1ε. SR-3029 also blocks CDK6/cyclin D3, CDK6/cyclin D1, CDK4/cyclin D3, CDK4/cyclin D1 and FLT3, with IC50s of 427, 428, 368, 576, and 3000 nM, respectively. SR-3029 shows inhibitory effects on A375 cells, with an EC50 of 86 nM[1]. CK1δ is a necessary and sufficient driver of Wnt/β-catenin signaling in human breast cancer. SR-3029 shows less potent activities against MCF7 and T47D breast cancer cells and the MCF10A cell line, which express low amounts of CK1δ[2].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.
    體內(nèi)研究
    (In Vivo)

    SR-3029 (20 mg/kg daily i.p.) exibits anti-tumor effects in rthotopic MDA-MB-231, MDA-MB-468 (TNBC), SKBR3 and BT474 (HER2+) tumor xenografts with no overt toxicity in mice. SR-3029 (20 mg/kg daily i.p.) also effectively inhibits the growth of tumor in primary patient-derived xenograft (PDX) models. In addition, SR-3029 (20 mg/kg, i.p.) strongly reduces the expression of nuclear β-catenin in tumors of mice[2].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.
    分子量

    480.45

    Formula

    C23H19F3N8O
    CAS 號(hào)
    性狀

    固體

    顏色

    White to pink

    運(yùn)輸條件

    Room temperature in continental US; may vary elsewhere.
    儲(chǔ)存方式
    Powder -20°C 3 years
    4°C 2 years
    In solvent -80°C 2 years
    -20°C 1 year
    溶解性數(shù)據(jù)
    細(xì)胞實(shí)驗(yàn)： 

    DMSO 中的溶解度 : ≥ 30 mg/mL (62.44 mM; 吸濕的 DMSO 對(duì)產(chǎn)品的溶解度有顯著影響，請(qǐng)使用新開封的 DMSO)

    * "≥" means soluble, but saturation unknown.

    配制儲(chǔ)備液
    濃度 溶劑體積 質(zhì)量 1 mg 5 mg 10 mg
    1 mM 2.0814 mL 10.4069 mL 20.8138 mL
    5 mM 0.4163 mL 2.0814 mL 4.1628 mL
    查看完整儲(chǔ)備液配制表

    * 請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲(chǔ)備液；一旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。
    儲(chǔ)備液的保存方式和期限：-80°C, 2 years; -20°C, 1 year。-80°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?年內(nèi)使用， -20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?年內(nèi)使用。

    • 摩爾計(jì)算器

    • 稀釋計(jì)算器

    Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

    質(zhì)量
    =
    濃度
    ×
    體積
    ×
    分子量 *

    Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

    This equation is commonly abbreviated as: C1V1 = C2V2

    濃度 (start)

    C1

    ×
    體積 (start)

    V1

    =
    濃度 (final)

    C2

    ×
    體積 (final)

    V2

    動(dòng)物實(shí)驗(yàn)：

    請(qǐng)根據(jù)您的 實(shí)驗(yàn)動(dòng)物和給藥方式 選擇適當(dāng)?shù)娜芙夥桨浮?

    以下溶解方案都請(qǐng)先按照 In Vitro 方式配制澄清的儲(chǔ)備液，再依次添加助溶劑：
    ——為保證實(shí)驗(yàn)結(jié)果的可靠性，澄清的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的工作液，建議您現(xiàn)用現(xiàn)配，當(dāng)天使用；
    以下溶劑前顯示的百分比是指該溶劑在您配制終溶液中的體積占比；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的方式助溶

    • 方案 一

      請(qǐng)依序添加每種溶劑： 10% DMSO    40% PEG300    5% Tween-80    45% Saline

      Solubility: ≥ 2.08 mg/mL (4.33 mM); 澄清溶液

      此方案可獲得 ≥ 2.08 mg/mL（飽和度未知）的澄清溶液。

      以 1 mL 工作液為例，取 100 μL 20.8 mg/mL 的澄清 DMSO 儲(chǔ)備液加到 400 μL PEG300 中，混合均勻；再向上述體系中加入 50 μL Tween-80，混合均勻；然后再繼續(xù)加入 450 μL 生理鹽水 定容至 1 mL。

      生理鹽水的配制：將 0.9 g 氯化鈉，溶解于 ddH?O 并定容至 100 mL，可以得到澄清透明的生理鹽水溶液。
    • 方案 二

      請(qǐng)依序添加每種溶劑： 10% DMSO    90% Corn Oil

      Solubility: ≥ 2.08 mg/mL (4.33 mM); 澄清溶液

      此方案可獲得 ≥ 2.08 mg/mL（飽和度未知）的澄清溶液，此方案實(shí)驗(yàn)周期在半個(gè)月以上的動(dòng)物實(shí)驗(yàn)酌情使用。

      以 1 mL 工作液為例，取 100 μL 20.8 mg/mL 的澄清 DMSO 儲(chǔ)備液加到 900 μL玉米油中，混合均勻。

    動(dòng)物溶解方案計(jì)算器
    請(qǐng)輸入動(dòng)物實(shí)驗(yàn)的基本信息：

    給藥劑量

    mg/kg

    動(dòng)物的平均體重

    g

    每只動(dòng)物的給藥體積

    μL

    動(dòng)物數(shù)量

    只
    由于實(shí)驗(yàn)過程有損耗，建議您多配一只動(dòng)物的量
    請(qǐng)輸入您的動(dòng)物體內(nèi)配方組成：
    %
    DMSO +
    % 
    +
    %
    Tween-80 +
    %
    Saline
    如果您的動(dòng)物是免疫缺陷鼠或者體弱鼠，建議 DMSO 中的在最后工作液體系中的占比盡量不超過 2%。
    方案所需 助溶劑 包括：DMSO， ，均可在 MCE 網(wǎng)站選購(gòu)。 ，Tween 80，均可在 MCE 網(wǎng)站選購(gòu)。
    計(jì)算結(jié)果
    工作液所需濃度 : mg/mL
    儲(chǔ)備液配制方法 : mg 藥物溶于 μL  DMSO（母液濃度為 mg/mL）。
    您所需的儲(chǔ)備液濃度超過該產(chǎn)品的實(shí)測(cè)溶解度，以下方案僅供參考，如有需要，請(qǐng)與 MCE 中國(guó)技術(shù)支持聯(lián)系。
    動(dòng)物實(shí)驗(yàn)體內(nèi)工作液的配制方法 : 取 μL DMSO 儲(chǔ)備液，加入 μL 。 μL ，混合均勻至澄清，再加 μL Tween 80，混合均勻至澄清，再加 μL 生理鹽水。
    連續(xù)給藥周期超過半月以上，請(qǐng)謹(jǐn)慎選擇該方案。
    請(qǐng)確保第一步儲(chǔ)備液溶解至澄清狀態(tài)，從左到右依次添加助溶劑。您可采用超聲加熱 （超聲清洗儀，建議頻次 20-40 kHz），渦旋吹打等方式輔助溶解。
    純度 & 產(chǎn)品資料

    純度: 99.73%

    參考文獻(xiàn)
    Kinase Assay
    [1]

    Briefly, final assay concentrations for CK1δ, Ulight peptide substrate (ULight-Topo-Ila(Thr1342) peptide) and ATP are 2 nM, 200 nM and 20 μM respectively. The reaction is performed at room temperature in a 10 μL final volume (384-well low volume plate) containing the following: 50 mM Hepes, pH 7.5, 5 mM MgCl2, 0.1 mg/mL bovine serum albumin, 1 mM dl-dithiothreitol, 0.01% Triton X-100 and 1% DMSO. After 10 min, the reaction is terminated by addition of 10 μL of 4 nM Eu-anti-p-Topo-Ila in Lance Detection Buffer. The fluorescent signal is detected using a plate reader. 10 point does-response curves with 3-fold dilutions starting from 10 μM for each compound (SR-3029) is generated in duplicate and data fit to a four parameter logistic[1].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.
    Cell Assay
    [1]

    Human A375 melanoma cells are cultured in Dulbecco's Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum, 1% penicillin/streptomycin and 1× MEM Non-Essential Amino Acids at 37°C, 5% CO2. To evaluate the anti-proliferative activity of newly synthesized CK1δ/ε inhibitors, each compound (SR-3029) is subjected to MTT assays against A375 melanoma cells and their EC50 values are determined. Briefly, A375 melanoma cells are plated into a 96-well plate and treated with a series of concentrations of each new inhibitor, vehicle (DMSO) or with SR-3029 or SR-1277 (positive controls). MTT assays are performed four days after treatment and data are analyzed using the GraphPad Prism5[1].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.
    Animal Administration
    [2]

    Stable pools of MDA-MB-231-Luc, MDA-MB-231, MDA-MB-468, SKBR3, or BT474 cells are established by injection of 2 × 106 cancer cells into the mammary fat pads of 6-week-old female athymic nude mice. Establishment of BCM-4013 patient-derived xenografts is performed. Briefly, fresh xenograft tumor fragments (～1 mm3) are transplanted into the cleared mammary fat pad of recipient SCID/Bg mice. Mice are treated with SR-3029 or vehicle (10:10:80, DMSO:Tween-80:Water) at 20 mg/kg daily by i.p. injection. Tumor volumes are measured as the indicated intervals using calipers or by luminescence imaging with the IVIS 100 imager after subcutaneous injection of luciferin (15 mg/mL). Average radiance (p/s/cm2/sr) is determined from tumor region-of-interest (ROI) using Living-Image analysis software[2].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.
    參考文獻(xiàn)

    完整儲(chǔ)備液配制表

    * 請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲(chǔ)備液；一旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。
    儲(chǔ)備液的保存方式和期限：-80°C, 2 years; -20°C, 1 year。-80°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?年內(nèi)使用， -20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?年內(nèi)使用。

    可選溶劑 濃度 溶劑體積 質(zhì)量 1 mg 5 mg 10 mg 25 mg
    DMSO 1 mM 2.0814 mL 10.4069 mL 20.8138 mL 52.0345 mL
    5 mM 0.4163 mL 2.0814 mL 4.1628 mL 10.4069 mL
    10 mM 0.2081 mL 1.0407 mL 2.0814 mL 5.2035 mL
    15 mM 0.1388 mL 0.6938 mL 1.3876 mL 3.4690 mL
    20 mM 0.1041 mL 0.5203 mL 1.0407 mL 2.6017 mL
    25 mM 0.0833 mL 0.4163 mL 0.8326 mL 2.0814 mL
    30 mM 0.0694 mL 0.3469 mL 0.6938 mL 1.7345 mL
    40 mM 0.0520 mL 0.2602 mL 0.5203 mL 1.3009 mL
    50 mM 0.0416 mL 0.2081 mL 0.4163 mL 1.0407 mL
    60 mM 0.0347 mL 0.1734 mL 0.3469 mL 0.8672 mL
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      Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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    產(chǎn)品名稱：
    SR-3029
    目錄號(hào)：
    HY-100011
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